OP0272 PREDNISONE USE AND THE INCIDENCE OF HYPERGLYCEMIA OR DIABETES IN PATIENTS WITH RHEUMATOID ARTHRITIS; A 10-YEAR SUB ANALYSIS OF THE BeSt STUDY.
Authors: J. van der Pol, S. A. Bergstra, T. Huizinga, C. Allaart
Journal: Annals of the Rheumatic Diseases (2022)

Background Use of prednisone in rheumatoid arthritis has been questioned because it may trigger side effects such as hyperglycemia and diabetes. Objectives To assess whether in RA the use of prednisone is associated with the development of hyperglycemia and diabetes. Methods The BeSt study is a multicenter, assessor-blinded randomized controlled 10-years follow-up trial in 508 non-diabetic early RA patients. Patients were randomised to 4 dynamic DMARD treatment strategy groups: 1) sequential monotherapy, 2) step-up combination therapy, 3) initial combination therapy including prednisone (60 mg/day, tapered to 7.5 mg/day in 7 weeks) and 4) initial combination therapy with infliximab. In groups 1, 2 and 4, prednisone had a maximum dose of 7.5 mg/day by protocol. Treatment was steered at disease activity score (DAS) ≤2.4. We performed a GEE over time to assess whether current prednisone use or cumulative prednisone dose were associated with hyperglycemia (glucose levels ≥7.8) and cox regression analyses to investigate the relationship between cumulative prednisone dose, previous prednisone use and diabetes (defined as either use of anti-diabetic medication or two instances of a glucose ≥ 11.1), assessed at 3-monthly visits. All analyses were adjusted for potential confounders. Results In total, 33/508 patients (6.5%) developed diabetes during the trial; 12 of these (36%) had received prior treatment with prednisone (any dose). Median (IQR) duration of prednisone use in all 508 patients was 9 (15) months and cumulative doses ranged from 0 to 27942 mg. The mean cumulative dose ranged from 55.5 mg in group 1 to 6170.0 mg in group 3. Previous prednisone use nor cumulative prednisone dose was associated with hyperglycemia or diabetes, with effect sizes ranging from a hazard ratio of 0.588 (95% CI 0.285; 1.21) for the association between any prednisone dose and diabetes to an odds ratio of 1.04 (95% CI 0.978; 1.13) for the association between cumulative prednisone dose and diabetes (Table 1). To identify potential causes for these results, we investigated the relationship between DAS and the same outcomes. We found a higher DAS was significantly associated with development of diabetes, but not with hyperglycemia. Table 1. The relationship between prednisone dose, DAS and glucose levels, hyperglycemia and diabetes GEE hyperglycemia* OR 95% CI Any prednisone dose 1 0.949 0.805; 1.12 Cumulative dose 1 1.04** 0.978; 1.13 DAS 2 1.24 0.842; 1.85 Cox Regression diabetes (any of the definitions ) HR 95% CI Any prednisone dose 3 0.588 0.285; 1.21 Cumulative dose 3 0.996** 0.960; 1.03 DAS 2 1.60 1.13; 2.26 CI: confidence interval, GEE: Generalized Estimating Equations, OR: odds ratio, HR: hazard ratio, DAS: disease activity* hyperglycemia: glucose level above 7.8 mmol/L; diabetes: random glucose level above 11.1 mmol/L at at least two time points** odds ratio per 500mg cumulative prednisone increase: 1 adjusted for DAS, age, diabetes and BMI: 2 adjusted for cumulative prednisone dose, age, gender and BM: 3 adjusted for DAS, age and BMI Conclusion In early RA patients, cumulative dose nor any previous prednisone use was associated with the risk of hyperglycemia or diabetes. A higher DAS was significantly associated with increased risk of developing diabetes. Potential risks of prednisone may have been mitigated by suppression of DAS. Disclosure of Interests Joy van der Pol: None declared, Sytske Anne Bergstra Grant/research support from: Pfizer, Thomas Huizinga: None declared, Cornelia Allaart Grant/research support from: The BeSt study was supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V.